Intra-individual variability of the metabolic effect of inhaled insulin together with an absorption enhancer

OBJECTIVE - To study the metabolic effect and the variability of the effect elicited by inhalation of 87.2 U insulin powder combined with an absorption enhancer. The metabolic effect was compared with that of 10.2 U regular insulin injected subcutaneously and of 5.5 U regular insulin given intravenously. RESEARCH DESIGN AND METHODS - In this single-center open euglycemic glucose clamp study, 13 healthy male volunteers received 5 insulin administrations on separate study days: once as an intravenous dose, once as a subcutaneous injection, and 3 times by inhalation, in randomized order. Glucose infusion rates (GIRs) necessary to keep blood glucose concentrations constant at 5.0 mmol/l were determined over an 8-h period after administration. RESULTS - After inhalation of the insulin powder aerosol, the onset of action was substantially more rapid than after subcutaneous insulin injection, and maximal action was reached earlier (86 +/- 47 vs. 182 +/- 53 min, P < 0.0001). The maximal glucose infusion rate after inhalation of insulin was comparable to that after subcutaneous insulin injection (9.2 +/- 2.6 vs. 8.8 +/- 2.8 mg . kg(-1) . min(-1), NS). The metabolic effect in the first 2 h after inhalation was significantly greater than that after subcutaneous insulin injection (amount of glucose infused: 0.88 +/- 0.25 vs. 0.59 +/- 0.20 g . kg(-1) . 120 min(-1), P < 0.0001). However, the total metabolic effect after inhalation and subcutaneous injection was comparable (2.50 +/- 0.76 vs. 2.56 +/- 0.69 g . kg(-1) . 480 min(-1), NS). The relative bioefficacy of inhaled insulin calculated in relation to the data from the subcutaneous insulin application was 12.0 +/- 3.5% (absolute bioefficacy 10.1 +/- 3.1%) but was highest in the first 2 h after application (18.5 +/- 3.7%; absolute bioefficacy 8.2 +/- 4.1%). The intraindividual variability of the metabolic response induced by insulin inhalation was 14 +/- 9% for the maximal glucose infusion rate, 15 +/- 10% for the time-to-maximal effect, and 16 +/- 12% for thr total amount of glucose infused. CONCLUSIONS - This feasibility study shows that inhaled insulin with an absorption enhancer has a pronounced metabolic effect compared with the results of a previous study of inhaled insulin without an enhancer. The intraindividual variability of the metabolic effect was comparable with that of inhaled and subcutaneously injected insulin.